Evolutionarily Conserved Function of a Viral MicroRNA
Evolutionarily Conserved Function of a Viral MicroRNA
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DOI：
10.1128/jvi.01144-08
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发表时间：
2008-10-01
影响因子：
5.4
通讯作者：
Sullivan, C. S.
中科院分区：
文献类型：
--
作者：
Seo, G. J.;Fink, L. H. L.;Sullivan, C. S.
microRNA（miRNAs）是基因表达的有效RNA调节因子。一些病毒编码miRNAs，大多数功能未知。大多数病毒miRNAs是不保守的，是否有任何保守的功能仍不清楚。在这里，我们报告说，两个人类多瘤病毒与严重疾病的免疫功能低下的个人，JC病毒和BK病毒，编码的miRNA与猴多瘤病毒猿猴病毒40 miRNA的功能相同。这些miRNA在感染后期表达，以自动调节早期基因表达。我们表明，从前体miRNA发夹的两个臂产生的miRNA在指导早期mRNA的切割方面是活跃的。这一发现表明，尽管miRNA种子区域存在多种差异，但主要靶标（早期mRNA）和功能（早期基因表达的下调）在灵长类多瘤病毒编码的miRNA中是进化保守的。此外，我们发现这些miRNAs在诊断为多瘤病毒相关疾病的个体中表达，表明它们有可能作为治疗干预的靶点。
MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus and BK virus, encode miRNAs with the same function as that of the monkey polyomavirus simian virus 40 miRNAs. These miRNAs are expressed late during infection to auto-regulate early gene expression. We show that the miRNAs generated from both arms of the pre-miRNA hairpin are active at directing the cleavage of the early mRNAs. This finding suggests that despite multiple differences in the miRNA seed regions, the primary target (the early mRNAs) and function ( the downregulation of early gene expression) are evolutionarily conserved among the primate polyomavirus-encoded miRNAs. Furthermore, we show that these miRNAs are expressed in individuals diagnosed with polyomavirus-associated disease, suggesting their potential as targets for therapeutic intervention.